Abstract
Aims
To evaluate endoscopic healing in the ustekinumab (UST) induction (UNITI-1&2) & maintenance (IM-UNITI) phase 3 studies.
Methods
Substudy patients (pts) had colonoscopies at baseline (UNITI Wk0), then 8 & 52 weeks later (IM-UNITI Wk44). Video-endoscopies were centrally read by a single blinded reader for ulcerations & SES-CD. In UNITI, pts received one IV dose (UST 130mg, UST ~6mg/kg, or PBO). Pts with clinical response [CR] (CDAI drop≥100) in UNITI were re-randomized to subcutaneous (SC) PBO or UST 90mg (q12w or q8w) [primary randomized IM-UNITI population]. Non-randomized pts were added to the pooled IM-UNITI population: UST IV non-responders - SC UST 90mg, then SC UST 90mg q8w if in CR 8wks later; PBO IV non-responders - UST IV 130mg, then SC UST 90mg q12w if in CR 8wks later; PBO induction responders - PBO throughout. Pts required SES-CD ≥3 at UNITI Wk0 to be included. Primary outcome: Change in SES-CD at UNITI Wk8 (combined UST vs PBO). IM-UNITI Wk44 efficacy was evaluated for both the IM-UNITI populations.
Results
At wk8, UST reduced SES-CD significantly more vs PBO. Results were similar across UST doses, studies, & other endpoints (Table 1a). At IM-UNITI Wk44, in the primary randomized IM-UNITI population trends favoured UST vs PBO maintenance (especially UST 90mg q8w) but small sample sizes (UST n=46; PBO n=24) limited conclusions. In the post-hoc pooled IM-UNITI population (Table 1b), trends supporting UST maintenance were favourable, especially 90mg q8w.
Conclusions
The endoscopy substudy primary endpoint was met: One IV UST dose significantly reduced SES-CD vs PBO, as early as Wk8. More pts receiving UST maintenance achieved wk44 endpoints vs PBO. These data support efficacy of UST in inducing & maintaining endoscopic healing in CD.
(Table 1a) Week 8 Results from UNITI-1/2
| PBO (N=97) | UST (N=155) | |
|---|---|---|
| SES-CD Change from BL, mean (SD)§ | -0.7 (4.97) | -2.8 (8.10)* |
| Clinically meaningful endoscopic improvement1 | 29.9% | 47.7%* |
| Endoscopic Response2 | 13.4% | 20.6% |
| Endoscopic Remission3 | 4.1% | 7.7% |
| Mucosal Healing4 | 4.1% | 9.0% |
(Table 1b) IM-UNITI Week 44 Results
| PBO (N=51) | 90mg q12w (N=47) | 90mg q8w (N=74) | |
|---|---|---|---|
| SES-CD Change from BL, mean (SD) | -2.0 (5.35) | -1.5 (4.22) | -3.8 (6.02) |
| Clinically meaningful endoscopic improvement1 | 27.5% | 29.8% | 48.6%* |
| Endoscopic Response2 | 4.2% | 5.9% | 24.1%* |
| Endoscopic Remission3 | 9.8% | 12.8% | 20.3% |
| Mucosal Healing4 | 9.8% | 12.8% | 21.6% |
*P ˂0.05 §Primary endpoint
1SES-CD reduction ≥3 from UNITI BL
2SES-CD reduction ≥50% from UNITI BL
3SES-CD ≤2
4No ulcerations
Funding Agencies
Janssen Research & Development, LLC